Heme Oxygenase-1 Induction by Blood-Feeding Arthropods Controls Skin Inflammation and Promotes Disease Tolerance
| Autor: | Bianca M. Nagata, Tiago D. Serafim, Fabiano Oliveira, Ian N. Moore, Eva Iniguez, Maria M. Disotuar, Claudio Meneses, Daniel E. Sonenshine, Valéria M. Borges, Shaden Kamhawi, Miguel P. Soares, Silvia Cardoso, Pedro Cecilio, Waldionê de Castro, Ranadhir Dey, Subir Karmakar, Jesus G. Valenzuela, Hira L. Nakhasi, Joshua R. Lacsina, Thiago DeSouza-Vieira |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Vector Borne Diseases Inflammation Dermatitis Biology Isozyme General Biochemistry Genetics and Molecular Biology Microbiology 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine parasitic diseases medicine Animals Heme Arthropods Leishmaniasis chemistry.chemical_classification Leishmania Insect Bites and Stings Blood meal Erythrophagocytosis 3. Good health Heme oxygenase Mice Inbred C57BL 030104 developmental biology Enzyme Culicidae chemistry Female medicine.symptom CD163 030217 neurology & neurosurgery Heme Oxygenase-1 |
| Zdroj: | Cell Reports |
| ISSN: | 2211-1247 |
| Popis: | Hematophagous vectors lacerate host skin and capillaries to acquire a blood meal, resulting in leakage of red blood cells (RBCs) and inflammation. Here, we show that heme oxygenase-1 (HO-1), a pleiotropic cytoprotective isoenzyme that mitigates heme-mediated tissue damage, is induced after bites of sand flies, mosquitoes, and ticks. Further, we demonstrate that erythrophagocytosis by macrophages, including a skin-residing CD163+CD91+ professional iron-recycling subpopulation, produces HO-1 after bites. Importantly, we establish that global deletion or transient inhibition of HO-1 in mice increases inflammation and pathology following Leishmania-infected sand fly bites without affecting parasite number, whereas CO, an end product of the HO-1 enzymatic reaction, suppresses skin inflammation. This indicates that HO-1 induction by blood-feeding sand flies promotes tolerance to Leishmania infection. Collectively, our data demonstrate that HO-1 induction through erythrophagocytosis is a universal mechanism that regulates skin inflammation following blood feeding by arthropods, thus promoting early-stage disease tolerance to vector-borne pathogens. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|